Effects of desferrioxamine on eicosanoid production in two intact cell systems

Desferrioxamine is an iron-chelating agent used in the treatment of iron overload. It is a powerful inhibitor of iron-dependent radical reactions and has been used to test for the involvement of such reactions in animal models of human disease. Recent proposals that desferrioxamine inhibits lipoxygenase and stimulates cyclo-oxygenase were examined by testing its action upon eicosanoid production in rat caecal fragments and elicited rat peritoneal leukocytes. Under certain experimental conditions, higher concentrations of desferrioxamine (up to 0.5 mM) enhanced eicosanoid production in leukocytes. Desferrioxamine concentrations greater than or equal to 500 microM also stimulated cyclo-oxygenase activity in caecal fragments. Although these results show that high concentrations of desferrioxamine can augment eicosanoid production under certain circumstances, the effects are likely not to be significant therapeutically in view of the concentrations of desferrioxamine achieved during in vivo use in humans.